This randomized phase III trial studies temozolomide and radiation therapy to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma (gliosarcoma closed to accrual as of 07-13-10). Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.

Overall survival [ Time Frame: From randomization to death due to any cause, assessed up to 4 years ] [ Designated as safety issue: No ]

Estimated using the Kaplan-Meier method and differences between treatment arms will be tested in the log rank test (Mantel 1966).

Progression-free survival [ Time Frame: From randomization to progression or death, whichever occurs first, assessed up to 4 years ] [ Designated as safety issue: No ]

Estimated using the Kaplan-Meier method and differences between treatment arms will be tested in the log rank test (Mantel 1966).

Secondary Outcome Measures:

Incidence of treatment-related toxicity as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]

Differences in observed severities of toxicities (grade 3+) between groups will be tested using a chi square test.

Other Outcome Measures:

Quality of life measured by the MDASI-BT and EORTC QLQ-C30/BCM20 [ Time Frame: Up to 10 weeks after registration ] [ Designated as safety issue: No ]

The mean scores from different tools will be calculated at baseline, 6 weeks, and 10 weeks after registration; the arms with and without bevacizumab will be compared using the two-sample t-test. If the parametric assumptions are not met, then the Mann-Whitney test will be used. Longitudinal data analysis will also be performed to change trend of scores over time across the two treatment arms using hierarchical formulation of the linear mixed model. The model will include initial performance status, age, and type of surgery.

Neurocognitive function measured by the Hopkins Verbal Learning Test-Revised [ Time Frame: Up to 10 weeks after registration ] [ Designated as safety issue: No ]

The cumulative incidence approach will be used to estimate the median time to neurocognitive failure to account for the competing risks of disease progression and death. Gray's test will be used to test for a statistically significant difference in the distribution of neurocognitive failure times.

Multivariate analysis will be performed using the Cox proportional hazard model for both outcomes to determine if molecular profile is an independent prognostic factor and possibly a predictive factor for the use of bevacizumab.

Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide PO QD for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide.

Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide.

Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient size for analysis of O-6-methylguanine-DNA methyltransferase (MGMT) and determination of molecular profile

Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; at least 1 cubic centimeter of tissue composed primarily of tumor must be present

Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy is not allowed because it will not provide sufficient tissue for MGMT analysis

The tumor tissue should be sent as soon as possible to maximize the likelihood of eligibility; tumor tissue should be submitted by 4 weeks after the surgical procedure so that the study registration and treatment can commence by the mandatory 5 week post-surgery outer limit

Sites must submit tissue directly to Dr. Aldape in order to obtain the MGMT analysis; patients from sites not following protocol-specified process for obtaining MGMT results will be made ineligible

The tumor must have a supratentorial component

History/physical examination within 14 days prior to step 2 registration

The patient must have recovered from the effects of surgery, postoperative infection, and other complications before step 2 registration

A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively prior to the initiation of radiotherapy; the postoperative scan must be performed within 28 days prior to step 1 registration

An MRI or computed tomography (CT) scan (potentially in addition to the postoperative scan) must be obtained within 10 days prior to the start of radiation therapy and must not demonstrate significant postoperative hemorrhage defined as > 1 cm diameter of blood; if > 1 cm of acute blood is detected, the patient will be ineligible for this trial; the radiation planning MRI or CT scan may be used to determine presence of hemorrhage

Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided pre- and postoperative contrast-enhanced CT scans are obtained and are of sufficient quality; preoperative and postoperative scans must be the same type; such patients cannot be enrolled into the advanced imaging component

Documentation of steroid doses within 14 days prior to step 2 registration

Karnofsky performance status >= 70

Absolute neutrophil count (ANC) >= 1,800 cells/mm^3

Platelets >= 100,000 cells/mm^3

Hemoglobin >= 10.0 g/dL (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable)

Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable, except prior temozolomide or bevacizumab; prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted

Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields

Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to step 2 registration, with the exception of the craniotomy for tumor resection

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration

Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive

Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity

Any other major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy

Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Pregnant or lactating women

Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study

For American College of Radiology Imaging Network (ACRIN) 6686 Advanced Imaging: inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker)

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00884741